This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project is investigating the protein-protein interactions between the Alzheimer's peptide A-beta and alpha-B crystallin, which may mediate neurotoxicity in Alzheimer's disease. Western blots have provided some evidence for colocalization of A-beta and alpha-B-crystallin in AD deposits. Preliminary evidence indicates that alpha-B crystallin blocks A-beta fibril formation and potentiates the neurotoxicity of recombinant human A-beta 1-42. Experiments are now underway to identify Ab-aB crystallin crosslink signature(s) in vitro using purified proteins and mass spectrometry. If this proves successful, later experiments will explore the occurrence of such crosslinks in human tissue samples.